It is the long-range plan of this project to study steroid and xenobiotic metabolism and binding in target tissues with emphasis on hormonally-active chemicals. We have studied the placental transfer and fetal uptake of chemicals such as the PCBs, PBBS, cadmium, DES, and TCDD. The pharmacokinetics of these chemicals are studied in relation to possible developmental toxicity, emphasizing chemically-induced alterations in the perinatal imprinting of hepatic enzyme activity. The sequence of biochemical events leading to programmed responses in control and neonatally-treated animals are investigated so that predictions might be made regarding structure-activity relationships. The perinatal development of steroid receptors in the liver and brain are evaluated for their influence on the programming process. Results have shown that metabolites of PCBs that are readily hydroxylated accumulate in the fetal intestine following maternal exposures; whereas, concentrations of the biologically-persistent isomers increase markedly in most tissues immediately after birth as a function of milk transfer and redistribution from brown fat.